PXD019430

PXD019430 is an original dataset announced via ProteomeXchange.

Title	VAV3 in ERBB4-mediated cancer cell migration
Description	ERBB4 is a member of the epidermal growth factor receptor (EGFR)/ERBB subfamily of receptor tyrosine kinases that regulates cellular processes including proliferation, migration and survival. ERBB4 signaling is involved in embryogenesis and homeostasis of adult tissues, but also in human pathologies such as cancer, neurological disorders and cardiovascular diseases. A mass spectrometry screen revealed guanine nucleotide exchange factor (GEF) VAV3, an activator of Rho family GTPases, as a novel ERBB4-interacting protein in breast cancer cells. The ERBB4-VAV3-interaction was confirmed by targeted mass-spectrometry, coimmunoprecipitation experiments, and further defined by demonstrating that kinase activity and tyrosine residues 1022 and 1162 of ERBB4, as well as the intact phosphotyrosine-interacting SH2 domain of VAV3 were necessary for the interaction. ERBB4 was also shown to stimulate tyrosine phosphorylation of the VAV3 activation domain, which is required for GEF activity of VAV proteins. In addition to VAV3, also the other members of the VAV family, VAV1 and VAV2 were shown to coprecipitate with ERBB4. Analyses of the effects of overexpression of dominant-negative VAV3 constructs or downregulation of VAV3 expression by shRNAs in breast cancer cells demonstrated that active VAV3 was involved in ERBB4-stimulated migration. These findings define the VAV GTPases as novel effectors of ERBB4 activity in a signaling pathway relevant for cancer cell migration.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:07:41.873.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Johannes Merilahti
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-05-27 17:21:29	ID requested
1	2020-06-23 22:15:02	announced
⏵ 2	2024-10-22 05:07:42	announced	2024-10-22: Updated project metadata.

10.1074/jbc.ra119.010925;

Ojala VK, Knittle AM, Kirjalainen P, Merilahti JAM, Kortesoja M, Tvorogov D, Vaparanta K, Lin S, Kast J, Pulliainen AT, Kurppa KJ, Elenius K, The guanine nucleotide exchange factor VAV3 participates in ERBB4-mediated cancer cell migration. J Biol Chem, 295(33):11559-11571(2020) [pubmed]

submitter keyword: VAV3, Targeted analysis, PRM,ERBB4

Klaus Elenius
contact affiliation	Institute of Biomedicine, and Medicity Research Laboratories, University of Turku, Turku, Finland; Turku Bioscience Centre, University of Turku, and Åbo Akademi University, Turku, Finland
contact email	klaus.elenius@utu.fi
lab head
Johannes Merilahti
contact affiliation	Turku Bioscience University of Turku
contact email	johannes.merilahti@utu.fi
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/06/PXD019430

PRIDE project URI

• PRIDE
  1. PXD019430
     1. Label: PRIDE project
     2. Name: VAV3 in ERBB4-mediated cancer cell migration